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Antidepressant use during pregnancy and autism spectrum disorder.

Boukhris T, Sheehy O, Mottron L, Berard A. 2016. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Paediatr, 170 (2): 117-124.

Autism spectrum disorder (ASD) is a neurodevelopmental syndrome of increasing prevalence characterised by alterations in communication, language and social interactions, and by particular patterns of interests and behaviours. The causes of ASD remain unknown, although it likely involves both genetic and environmental factors.

Antidepressants (ADs) are widely used during gestation for the treatment of depression, with reported prevalence of usage during pregnancy being 4.5% in Canada and 13.3% in the United States. Gestational exposure to ADs has been associated with increased risk of spontaneous abortion, congenital malformation, prematurity, low birth weight, and neonatal withdrawal; however, discontinuation of ADs during pregnancy in women with severe depression has been associated with relapse. Accordingly, the management of depression during pregnancy is highly complex. Prior studies investigating the effect of AD use during pregnancy and risk of offspring developing ASD have produced conflicting results. The authors of the current study aimed to investigate the risk of ASD in children associated with AD use during pregnancy according to class of AD and trimester of exposure.

A Canadian register-based study was conducted from an ongoing population-based cohort, the Quebec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Quebec. A medical service database, the Public Prescription Drug Insurance database, a hospitalisation archive database and the Quebec Statistics database provided information on diagnoses, medical procedures, prescription drugs, birth weight and socioeconomic data. All full term (> 37 weeks gestation) singleton infants born between 1998 and 2009 were included in the study, provided prescription drug information was available for at least 12 months before and during pregnancy. AD exposure was defined as having at least 1 prescription anytime during pregnancy, or a prescription filled before pregnancy that crossed over with the first day of gestation, with exposure further defined according to trimester and specific AD classes.

Diagnosis of childhood ASD was defined as a medical service claim or hospitalisation with a diagnosis of ASD, including childhood autism, atypical autism, Asperger syndrome, and other pervasive development disorders.

Of the 145,456 full-term singleton infants born alive, 1054 (0.72%) had at least one diagnosis of ASD. The mean age of first diagnosis was 4.6 years and boys with ASD outnumbered girls by a ratio of about 4:1. In total, 3.2% of infants were exposed to ADs in utero, of which 88.9% were exposed during the first trimester and 53.5% were exposed during the second and/or third trimester. Of the infants exposed to ADs during the first trimester, 1.0% were diagnosed with ASD whilst 1.2% of infants exposed to ADs during the second and/or third trimester were diagnosed with ASD. After adjustment for potential confounders, use of ADs during the second and/or third trimester was statistically associated with increased risk of ASD. Use of ADs during the first trimester was not associated with increased risk of offspring ASD. Authors reported the use of SSRIs during the second and/or third trimester to be significantly associated with increased risk of ASD. No statistically significant observations were found with other classes of ADs, however the small numbers of exposed would limit such observations.

SSRIs are known to cross the placenta and can be found in amniotic fluid. Serotonin is known to modulate a number of prenatal and postnatal development processes, including cell division, neuronal migration, cell differentiation and synaptogenesis. The synthesis of serotonin in the brain of children with ASD is reported to develop atypically, with evidence of high levels of serotonin in blood platelets in individuals with ASD.

Authors note one of the strengths of the study is the 11-year follow up period; however, one of the limitations of this study and its results is the inclusion of AD exposure data for infants born until Dec 31 2009, which was the end of the follow-up period. With the mean age of first ASD diagnosis in this study being 4.6 years, many infants included in the AD exposure would not have developed enough to warrant investigations for ASD or first diagnosis. This may have reduced the prevalence of ASD for the study population, and limited the observations of relationship drawn between AD exposure and ASD prevalence. Furthermore, only full-term births were included in the study whilst both AD use during pregnancy and ASD have been associated with prematurity. The use of prescription-filling data for AD use during pregnancy may not reflect actual usage patterns.

Managing depression during pregnancy and the complexities of balancing maternal health needs and in utero drug exposure is challenging. Maternal antidepressant use during pregnancy has an important place; however, better understanding the effects of such interventions on the neurodevelopmental effects on offspring is required.

Jodie Tester

These abstracts are brief summaries of articles which have appeared in recent issues of herbal medicine journals, some of which may be held in the NHAA library.
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Author:Tester, Jodie
Publication:Australian Journal of Herbal Medicine
Article Type:Report
Geographic Code:8AUST
Date:Jun 1, 2016
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